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Efficacy of stress-response protease-deficient Salmonella enterica serovar Typhimurium as a candidate of live oral vaccine strain

应激反应蛋白酶缺陷型鼠伤寒沙门氏菌作为候选活口服疫苗株的功效

基本信息

批准号：
15590398
负责人：
MATSUI Hidenori
金额：
$ 1.92万
依托单位：
Kitasato University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590398/
关键词：
Salmonella vaccine stress response

项目摘要

The Lon protease-deficient Salmonella enterica serovar Typhimurium (CS2022) is immunogenic when given via the oral infection route in mice. In the present study, CS2022 continuously resided in the spleen of BALB/c mice with less than 10^2 CFU for up to 6 weeks after a single oral inoculation with 10^7 CFU of salmonellae. A significant increase in the serovar Typhimurium lipopolysaccharide (LPS)-specific IgG2a was detected in the serum at weeks 4, 6, and 13 after inoculation. In contrast, the LPS-specific IgG1 was detectable at weeks 6 and 13 after inoculation. The expression of IFN-γ mRNA in the spleens of these mice was significantly increased at weeks 4 and 6 after inoculation. In contrast, the expression of IL-4 mRNA was increased at week 6 after inoculation. As a result, oral inoculation with CS2022 protected mice against subsequent subcutaneous challenge with the virulent serovar Typhimurium. In addition, the inoculation was able to reduce the colonization of Listeria monocytogenes in the livers for at least 6 weeks after inoculation when it was administered via the subcutaneous infection route. Furthermore, peritoneal macrophages isolated from immunized mice at weeks 2, 4, and 6 after inoculation led to an increase in the intracellular killing activity against L.monocytogenes as well as against serovar Typhimurium. These findings suggest that oral immunization with CS2022 promoted the protective innate immunity associated with macrophages, and this rapid protective immunity might also be sufficient to eliminate the colonization of certain intracellular pathogens other than Salmonella for at least 6 weeks after immunization of mice.

Lon蛋白酶缺陷型鼠伤寒沙门氏菌（CS2022）通过小鼠经口感染途径给药时具有免疫原性。在本研究中，单次经口接种10^7 CFU沙门氏菌后，CS2022以低于10^2 CFU持续驻留在BALB/c小鼠脾脏中长达6周。在接种后第4、6和13周，在血清中检测到鼠伤寒血清型脂多糖（LPS）特异性IgG 2a显著增加。相反，LPS特异性IgG 1在接种后6周和13周可检测到。免疫后4周和6周，小鼠脾脏IFN-γ mRNA的表达显著增加。而IL-4 mRNA的表达在接种后6周开始增加。因此，口服接种CS2022保护小鼠免受随后的皮下攻击与强毒血清型鼠伤寒。此外，当通过皮下感染途径给药时，接种能够在接种后至少6周内减少肝脏中单核细胞增生李斯特菌的定殖。此外，在接种后第2、4和6周从免疫小鼠中分离的腹腔巨噬细胞导致对单核细胞增生李斯特菌以及鼠伤寒血清型的细胞内杀伤活性增加。这些发现表明，口服免疫CS2022促进了与巨噬细胞相关的保护性先天免疫，并且这种快速的保护性免疫也可能足以在小鼠免疫后至少6周内消除除沙门氏菌以外的某些细胞内病原体的定殖。

项目成果

期刊论文数量（102）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The DnaK/DnaJ chaperone machinery of Salmonella enterica serovar Typhimurium is essential for invasion of epithelial cells and survival in macrophages, leadin

鼠伤寒沙门氏菌的 DnaK/DnaJ 伴侣机制对于上皮细胞的侵袭和巨噬细胞的存活至关重要，

DOI：
发表时间：
2004
期刊：
Infect.Immun. 72・3
影响因子：
0
作者：
A.Takaya;T.Tomoyasu;H.Matsui;T.Yamamoto
通讯作者：
T.Yamamoto

Interaction of leptin with gastric myofibroblast transdifferentiation in Helicobacter pylori-infected Mongolian gerbils : effect of rebamipide.

瘦素与幽门螺杆菌感染的蒙古沙鼠胃肌成纤维细胞转分化的相互作用：瑞巴派特的作用。

DOI：
发表时间：
2003
期刊：
Alimentary Pharmacology and Therapeutics 18(Suppl.1)
影响因子：
0
作者：
A.Takaya;T.Tomoyasu;H.Matsui;T.Yamamoto;M.Eguchi et al.;M.Nakamura et al.;M.Nakamura et al.;M.Nakamura et al.
通讯作者：
M.Nakamura et al.

M.Eguchi, K.Monden, N.Miwa.: "Role of MAPK phosphorylation in cytoprotection by pro-Vrtamin C aganst oxidative stress-induced injuries in cultured cardiomyoblasts and perfused rat heart"J.Cell.Biochem.. 90・2. 219-226 (2003)

M.Eguchi、K.Monden、N.Miwa.：“MAPK 磷酸化在 Vrtamin C 前体细胞保护中的作用，对抗培养的成肌细胞和灌注大鼠心脏中氧化应激诱导的损伤”J.Cell.Biochem.. 90・2。 219-226 (2003)